Congenital cardiac malformations are being studied from the standpoint of the basic mechanisms (final common pathways) of their formation. A working hypothesis has been formulated from pilot studies on normal heart development and experimentally induced cardiac maldevelopment using a variety of teratogens (trypan blue, maternal diabetes, hypoxia). This hypothesis purports that an alteration in mucopolysaccharide metabolism early in organogenesis may constitute a key underlying mechanism leading to anomalous cardial septal development. It is proposed to compare the ultrastructural, ultracytochemical, histochemical, autoradiographic and biochemical changes in hearts of rat fetuses exposed to the above teratogens with those, if any, incurred by administering an established inhibitor of mucopolysaccharide synthesis - sodium salicylate. If morphologic and biochemical similarities are found, the hypothesis will be further tested by attempting to offset potential cardiac defects in embryos administered a teratogen by giving as countertherapy intra-amniotic injections of mucopolysaccharide precursors alone or combined with high energy nucleotide phosphates. When different cardiac teratogenic agents produce similar ultrastructural and biochemical changes as noted in pilot studies, it is essential to determine if a basic final common pathway is operative in order to track down the causation of clinical congenital defects.